Initial Treatment for Autoimmune Hepatitis
Start combination therapy with prednisone 30 mg/day (tapering to 10 mg/day over 4 weeks) plus azathioprine 1-2 mg/kg/day as the initial treatment for autoimmune hepatitis. 1, 2
Why Combination Therapy is Superior
Combination therapy produces significantly fewer corticosteroid-related side effects compared to prednisone monotherapy (10% versus 44%) while maintaining equivalent efficacy. 1, 3 This makes it the preferred regimen, especially in elderly patients who are at higher risk for steroid complications. 4
Specific Dosing Schedule
The standard induction regimen follows this taper: 1, 3
- Week 1: Prednisone 30 mg/day + Azathioprine 50 mg/day (US) or 1-2 mg/kg/day (Europe)
- Week 2: Prednisone 20 mg/day + Azathioprine (same dose)
- Weeks 3-4: Prednisone 15 mg/day + Azathioprine (same dose)
- Maintenance: Prednisone 10 mg/day + Azathioprine (same dose)
An alternative European approach starts prednisone alone for two weeks before adding azathioprine, particularly when bilirubin is below 6 mg/dL. 2
Treatment Duration and Monitoring
Continue treatment for at least 2 years and for at least 12 months after normalization of liver enzymes. 1, 2 The average duration of initial treatment is 18-24 months. 1, 3
Monitor response at 4-8 weeks after initiation—serum aminotransferases typically improve within 2 weeks of starting therapy. 3 Check aminotransferase levels monthly, as small decrements in prednisone dose can cause marked increases in enzyme levels. 3 Aim for complete normalization of both transaminases AND IgG levels, as persistent elevations predict relapse, ongoing histological activity, and progression to cirrhosis. 2
Special Populations Requiring Modified Approach
Patients with Cytopenia
Measure thiopurine methyltransferase (TPMT) activity before starting azathioprine to exclude homozygote TPMT deficiency. 1, 2 Use prednisone monotherapy in patients with severe pre-treatment cytopenia. 1 Only 0.3%-0.5% of the population has severe enzyme deficiency, making routine screening unnecessary unless cytopenia is present. 5
Non-Cirrhotic Patients at High Risk for Steroid Side Effects
Consider budesonide 9 mg/day plus azathioprine specifically in treatment-naive, non-cirrhotic patients with early-stage disease who have high risk for steroid complications (psychosis, poorly controlled diabetes, severe osteoporosis). 2 Do not use budesonide in cirrhotic patients due to loss of first-pass hepatic metabolism and safety concerns from portosystemic shunting. 6
Acute Severe Autoimmune Hepatitis
Treat immediately with high-dose intravenous corticosteroids (≥1 mg/kg) as early as possible. 2
Management of Treatment Failure
For non-responders after 2-3 years, increase to prednisone 60 mg daily alone or prednisone 30 mg daily with azathioprine 150 mg daily for at least 1 month. 5, 3 Alternative options for steroid-refractory cases include tacrolimus or cyclosporine. 1, 3
Prevention of Treatment Complications
All patients must receive: 1, 3, 2
- Calcium and vitamin D supplementation from treatment initiation
- DEXA scanning for bone mineral density at 1-2 year intervals
- Vaccination against hepatitis A and B early in susceptible patients
Severe complications (osteoporosis, vertebral compression, diabetes, cataracts, hypertension, psychosis) typically develop after 18 months of therapy at prednisone doses >10 mg daily. 3
Expected Outcomes and Relapse Management
80-90% of patients achieve biochemical improvement with transaminases normalizing within 6 months in most responders. 2 However, relapse occurs in 50-90% of patients within 12 months of stopping treatment. 1, 3, 2 After relapse, use long-term maintenance with azathioprine 2 mg/kg/day—87% of adult patients remain in remission during median follow-up of 67 months. 1, 3
Common Pitfall to Avoid
Do not aim for merely reducing aminotransferases to below two times the upper limit of normal—this outdated approach is insufficient. 6 Complete normalization of both transaminases and IgG levels should be the goal, as anything less predicts poor outcomes. 2